Weak association of anti-sperm antibodies and strong association of familial cryptorchidism/infertility with HLA-DRB1 polymorphisms in prepubertal Ukrainian boys.

Background: Cryptorchidism is a frequent syndrome occurring in 1-2% of males within the first year of age. Autoimmune reactions, particularly directed to testicular elements and/or spermatozoa have been found to be often associated with cryptorchidism. Therefore we investigated in this study the frequency of HLA class II alleles in order to recognize possible genetic predisposition for antisperm antibodies development in prepubertal boys with diagnosed cryptorchidism in Caucasoid population.

Methods: Sixty prepubertal boys with cryptorchidism and sixty healthy boys were examined for anti-sperm antibodies by indirect immunobead test as well as for their HLA-DRB1 and -DQB1 alleles using DNA obtained from peripheral blood leukocytes. The typing of HLA-DRB1 and -DQB1 was performed by using PCR-SSP low resolution method.

Results: Allele frequencies of HLA-DRB1 and HLA-DQB1 did not differ between boys with cryptorchidism and control boys. However, weakly significant differences in DRB1*04 (p corrected=0.0475) and DQB1*06 (p corrected=0.0385) were seen between cryptorchid patients with and without AsA, but none of these two patient groups differed significantly in HLA class II frequencies from controls except for AsA-negatives and HLA-DQB1*06 (p corrected=0.0247). On the other hand, comparison of cryptorchid boys with familial cryptorchidism and/or infertility to control boys revealed highly significant (p corrected=0.0006) difference in HLA-DRB*11 frequency, whereas boys with sporadic cryptorchidism did not differ from control. A much weaker, but still significant difference in DRB*11 frequency was also observed between boys with bilateral cryptorchidism and controls (p corrected=0.037), whereas patients with unilateral cryptorchidism were not different from control in frequency of any HLA-DRB1 or -DQB1 allele tested.

Conclusions: Predisposition to produce anti-sperm antibodies seems to be only weakly associated with HLA class II genes, although this question requires further study on much larger population sample. It is plausible that familial and sporadic cryptorchidism may present distinct genetic background. The same may, to lower extent, apply to bilateral and unilateral cryptorchidism.